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Click to Watch A Genomic Analysis of Predisposition to Systemic Autoimmunity

The Immunology Interest Group

Wednesday, March 23, 2011 4:15:00 PM EDT (-0400)

Ward Wakeland

Runtime 90 minutes

Completed

CC Grand Rounds Lecture Series:(1) PARP Inhibitors: How Successful Have We Been in Modulating DNA Damage? (2) The Evolving Role of PARP Inhibitors in Breast and Ovarian Cancers

CC Grand Rounds

For more information, visit:
http://www.cc.nih.gov/about/news/grcurrent.html

Wednesday, March 23, 2011 12:00:00 PM EDT (-0400)

(1) Shivaani Kummar, MD, Head, Early Clinical Trials Development, Office of the Director, Division of Cancer Treatment and Diagnosis, NCI (2) Elise C. Kohn, MD, Head, Medical Ovarian Cancer Clinic, and Head, Molecular Signaling Section, Medical Oncology Branch, Center for Cancer Research, NCI

Runtime 60 minutes

This event will be available for on-demand viewing in our Past Events archive as soon as possible, usually within a few days.

Completed

Workplace Ergonomics (NIH Only)

DOHS Seminar Series

The Office of Research Services, Division of Occupational Health and Safety in partnership with the Division of Amenities and Transportation Services Wellness Program is proud to present a new Seminar Series focused on Employee Workplace Health and Safety.

Join us for this new monthly seminar series. The first topic will feature office ergonomics by LT Jeremy Mason and Susan McDonald from the Division of Occupational Health and Safety. LT Mason and Ms. McDonald will provide tips on how to set up your work station to avoid neck, arm, or back discomfort while working at the computer.

LT Jeremy Mason is an industrial hygienist who has worked in the field of ergonomics for five years. Susan McDonald is a certified industrial hygienist who has worked in the field of ergonomics for nine years. Before coming to NIH, Ms. McDonald worked at the State Department, providing ergonomic evaluations and assistance to office workers. In addition to computer work station ergonomics, LT Mason and Ms. McDonald also provide assistance to laboratory employees with ergonomic concerns.

Wednesday, March 23, 2011 1:00:00 PM EDT (-0400)

LT. Jeremy Mason, Ms. Susan McDonald

Runtime 60 minutes

This event will be available for on-demand viewing in our Past Events archive as soon as possible, usually within a few days.

Completed

Alzheimer's Disease: From Genes to Novel Therapeutics

Alzheimer’s disease (AD) is strongly influenced by inheritance and genetic susceptibility as evidenced by numerous family and twin studies. Over the past two and a half decades, our laboratory has co-discovered the three early-onset familial AD genes, APP, PSEN1, and PSEN2, which can carry any of >200 fully penetrant mutations characterized by mendelian inheritance. For late-onset AD, the only well-established risk factor is the epsilon 4 variant of APOE, which increases risk by 3.7-fold in the heterozygous state and >10-fold when two copies are inherited. It has been estimated that 50-70% of the genetic variance of AD remains unexplained by the four established AD genes. We are engaged in two major efforts to identify the additional AD genes as part of our Alzheimer’s Genome Project funded by the Cure Alzheimer’s Fund. First, for published AD candidate genes, we have developed the AlzGene.org website, a comprehensive, online encyclopedia and database, which includes data on >650 AD candidate genes and >~3000 DNA variants that have been tested for association with AD. For all DNA variants tested in at least four independent samples (~300), AlzGene.org provides meta-analyses to determine the most promising AD candidate genes. These studies have led to over 40 candidate AD genes, including APOE, that yield significant results. However, the effects of these variants on risk are tiny compared to APOE (.75≤O.R.≤1.25).

We are currently exploring whether these associations are being driven by rare late-onset AD mutations in linkage disequilibrium with the disease-associated common variants. We found this to be the case for the APP alpha-secretase gene, ADAM10,in which we discovered two rare mutations that severely impair ADAM10 cleavage of APP both in vitro and in transgenic mice. Second, in a parallel effort, we have carried out several genome-wide association studies on >800 well-characterized late-onset AD families (NIMH and NCRAD samples) using Affymetrix genotyping arrays containing either one million (6.0) or 500,000 (5.0) genomic single nucleotide polymorphisms (SNPs) as well as arrays containing 20,000 coding SNPs. We have previously reported four novel loci that achieved genome-wide significance (besides APOE) including a novel gene on chromosome 14q, GWA-14q, the ataxin 1 gene, the innate immune system lectin gene, CD33, and the synaptic gene, DLGAP1.

Functional studies of the ATXN1 gene carried out both in vitro and in vivo in ATXN1 knockout mice show that ATXN1 can regulate Ab levels via modulation of beta-secretase. We will also present new data implicating Ab as an anti-microbial peptide in the innate immune system. These latter data in combination with several novel candidate genes emanating from the Alzheimer’s Genome Project suggest that innate immune system in the brain may play a central role in the etiology and pathogenesis of AD, raising new possibilities for novel drug discovery. Along these lines, I will present data on several promising therapeutics aimed at preventing and treating AD based on knowledge gained from AD genes.

The NIH Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide.

For more information, visit:
http://wals.od.nih.gov/

Wednesday, March 23, 2011 3:00:00 PM EDT (-0400)

Dr. Rudolph Tanzi, Harvard Medical School

Runtime 60 minutes

This event will be available for on-demand viewing in our Past Events archive as soon as possible, usually within a few days.